The impact of neuropsychological functioning and coping style on perceived stress in individuals with first-episode psychosis and healthy controls

Stress is implicated in the development and course of psychotic illness, but the factors that influence stress levels are not well understood. The aim of this study was to examine the impact of neuropsychological functioning and coping styles on perceived stress in people with first-episode psychosis (FEP) and healthy controls (HC). Thirty-four minimally treated FEP patients from the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, and 26 HC participants from a similar demographic area participated in the study. Participants completed a comprehensive neuropsychological test battery as well as the Coping Inventory for Stressful Situations (task-, emotion- and avoidance-focussed coping styles) and Perceived Stress Scale (PSS). Linear regressions were used to determine the contribution of neuropsychological functioning and coping style to perceived stress in the two groups. In the FEP group, higher levels of emotion-focussed and lower levels of task-focussed coping were associated with elevated stress. Higher premorbid IQ and working memory were also associated with higher subjective stress. In the HC group, higher levels of emotion-focussed coping, and contrary to the FEP group, lower premorbid IQ, working memory and executive functioning, were associated with increased stress. Lower intellectual functioning may provide some protection against perceived stress in FEP.

Cardiovascular disease is increased prior to onset of rheumatoid arthritis but not osteoarthritis: The population-based Nord-Trøndelag health study (HUNT)

Introduction: Patients with rheumatoid arthritis (RA) have increased risk of cardiovascular (CV) events. We sought to test the hypothesis that due to increased inflammation, CV disease and risk factors are associated with increased risk of future RA development. Methods: The population-based Nord-Trøndelag health surveys (HUNT) were conducted among the entire adult population of Nord-Trøndelag, Norway. All inhabitants 20 years or older were invited, and information was collected through comprehensive questionnaires, a clinical examination, and blood samples. In a cohort design, data from HUNT2 (1995-1997, baseline) and HUNT3 (2006-2008, follow-up) were obtained to study participants with RA (n = 786) or osteoarthritis (n = 3,586) at HUNT3 alone, in comparison with individuals without RA or osteoarthritis at both times (n = 33,567). Results: Female gender, age, smoking, body mass index, and history of previous CV disease were associated with self-reported incident RA (previous CV disease: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CV disease were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.23-2.36)) or restricting the analysis to cases with a hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.13-2.74)). History of previous CV disease was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). Conclusion: A history of previous CV disease was associated with increased risk of incident RA but not osteoarthritis.

Applying Keller’s brand equity model in a B2B context : limitations and an empirical test

It has been recognised that brands play a role in industrial markets, but to date a comprehensive model of business-to-business (B2B) branding does not exist, nor has there been an empirical study of the applicability of a full brand equity model in a B2B context. This paper is the first to begin to address these issues. The paper introduces the Customer- Based Brand Equity (CBBE) model by Kevin Keller (1993; 2001; 2003), and empirically tests its applicability in the market of electronic tracking systems for waste management. While Keller claims that the CBBE pyramid can be applied in a B2B context, this research highlights challenges of such an application, and suggests changes to the model are required. Assessing the equity of manufacturers’ brand names is more appropriate than measuring the equity of individual product brands as suggested by Keller. Secondly, the building blocks of Keller’s model appear useful in an organisational context, although differences in the subdimensions are required. Brand feelings appear to lack relevance in the industrial market investigated, and the pinnacle of Keller’s pyramid, resonance, needs serious modifications. Finally, company representatives play a role in building brand equity, indicating a need for this human element to be recognised in a B2B model.

Cross-talk of subchondral bone osteoblasts and articular cartilage chondrocytes : a new insight in understanding osteoarthritis pathogenesis

Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo atypical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. Collectively these findings indicate that the pathological changes typical of OA, involve alterations of the phenotypic properties of cells in both the subchondral bone and articular cartilage. However, the mechanism(s) by which these changes occur during OA development are not completely understood. The purpose of this project was to address the question of how subchondral bone osteoblasts (SBOs) and ACCs interact with each other with respect to regulation of respective cells’ phenotypic properties and in particular the involvement of mitogen activated protein kinase (MAPK) signalling pathways under normal and OA joint condition. We also endeavoured to test the influence of cross-talk between SBOs and ACCs isolated from normal and OA joint on matrix metalloproteinase (MMP) expression. For this purpose tissues from the knees of OA patients and normal controls were collected to isolate SBOs and ACCs. The cellular cross-talk of SBOs and ACCs were studied by means of both direct and indirect co-culture systems, which made it possible to identify the role of both membrane bound and soluble factors. Histology, immunohistochemistry, qRT-PCR, zymography, ELISA and western blotting were some of the techniques applied to distinguish the changes in the co-cultured vs. non co-cultured cells. The MAPK signalling pathways were probed by using targeted MAPK inhibitors, and their activity monitored by western blot analysis using phospho MAPK specific antibodies. Our co-culture studies demonstrated that OA ACCs enhanced the SBOs differentiation compared to normal ACCs. We demonstrated that OA ACCs induced these phenotypic changes in the SBOs via activating an ERK1/2 signalling pathway. The findings from this study thus provided clear evidence that OA ACCs play an integral role in altering the SBO phenotype. In the second study, we tested the influence of normal SBOs and OA SBOs on ACCs phenotype changes. The results showed that OA SBOs increased the hypertrophic gene expression in co-cultured ACCs compared to normal SBOs, a phenotype which is considered as pathological to the health and integrity of articular cartilage. It was demonstrated that these phenotype changes occurred via de-activation of p38 and activation of ERK1/2 signaling pathways. These findings suggest that the pathological interaction of OA SBOs with ACCs is mediated by cross-talking between ERK1/2 and p38 pathways, resulting in ACCs undergoing hypertrophic differentiation. Subsequent experiments to determine the effect on MMP regulation, of SBOs and ACCs cross-talk, revealed that co-culturing OA SBOs with ACCs significantly enhanced the proteolytic activity and expression of MMP-2 and MMP-9. In turn, co-culture of OA ACCs with SBOs led to abundant MMP-2 expression in SBOs. Furthermore, we showed that the addition of ERK1/2 and JNK inhibitors reversed the elevated MMP-2 and MMP-9 production which otherwise resulted from the interactions of OA SBOs-ACCs. Thus, this study has demonstrated that the altered interactions between OA SBOs-ACCs are capable of triggering the pathological pathways leading to degenerative changes seen in the osteoarthritic joint. In conclusion, the body of work presented in this dissertation has given clear in vitro evidence that the altered bi-directional communication of SBOs and ACCs may play a role in OA development and that this process was mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA.

Aggravation of ADAMTS and MMP production and ERK1/2 pathway in the interaction of osteoarthritic subchondral bone osteoblasts and articular cartilage chondrocytes : a possible pathogenic role in osteoarthritis

Introduction: Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMPs), play key roles in osteoarthritis (OA) development. The aim of the present study was to investigate if cross-talk between subchondral bone osteoblasts (SBOs) and articular cartilage chondrocytes (ACCs) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13, and also to test the possible involvement of mitogen activated protein kinase (MAPK) signaling pathway during this process. Methods: ACCs and SBOs were isolated from normal and OA patients. An in vitro co-culture model was developed to study the regulation of ADAMTS and MMPs under normal and OA joint cross-talk conditions. MAPK-ERK inhibitor, PD98059 was applied to delineate the involvement of specific pathway during this interaction process. Results: Indirect co-culture of OA SBOs with normal ACCs resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3 and MMP-9 in ACCs, whereas co-culture of OA ACCs led to increased MMP-1 and MMP-2 expression in normal SBOs. The upregulation of ADAMTS and MMPs under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway and the addition of the MAPK-ERK inhibitor, PD98059, reversed the overexpression of ADAMTS and MMPs in co-cultures. Conclusion: In summary, we believe, these results add to the evidence that in human OA, altered bi-directional signals transmitted between SBOs and ACCs significantly impacts the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMPs. Furthermore, we have demonstrated for the first time that this altered cross-talk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.

Test of a model of the effects of parental illness on youth and family functioning

Objective: Parental illness (PI) may have adverse impacts on youth and family functioning. Research in this area has suffered from the absence of a guiding comprehensive framework. This study tested a conceptual model of the effects of PI on youth and family functioning derived from the Family Ecology Framework (FEF; Pedersen & Revenson, 2005). Method. A total of 85 parents with multiple sclerosis and 127 youth completed questionnaires at Time 1 and 12 months later at Time 2. Results. Structural equation modeling results supported the FEF with regards to physical-illness disability. Specifically, the proposed mediators (role redistribution, stress, and stigma) were implicated in the processes that link parental disability to several domains of youth adjustment. The results suggest that the effects of parental depression (PD) are not mediated through these processes; rather, PD directly affects family functioning, which in turn mediates the effects onto youth adjustment. Family functioning further mediated between PD and youth well-being and behavioral-social difficulties. Conclusions. Although results support the effects of parental-illness disability on youth and family functioning via the proposed mediational mechanisms, the additive effects of PD on youth physical and mental health occur through direct and indirect (via family functioning) pathways, respectively.

Reducing aggression on our roads : testing a comprehensive model of aggressive driving

Background: Trauma resulting from traffic crashes poses a significant problem in highly motorised countries. Over a million people worldwide are killed annually and 50 million are critically injured as a result of traffic collisions. In Australia, road crashes cost an average of $17 billion annually in personal loss of income and quality of life, organisational losses in productivity and workplace quality, and health care costs. Driver aggression has been identified as a key factor contributing to crashes, and many motorists report experiencing mild forms of aggression (e.g., rude gestures, horn honking). However despite this concern, driver aggression has received relatively little attention in empirical research, and existing research has been hampered by a number of methodological and conceptual shortcomings. Specifically, there has been substantial disagreement regarding what constitutes aggressive driving and a failure to examine both the situational factors and the emotional and cognitive processes underlying driver aggression. To enhance current understanding of aggressive driving, a model of driver aggression that highlights the cognitive and emotional processes at play in aggressive driving incidents is proposed. Aims: The research aims to improve current understanding of the complex nature of driver aggression by testing and refining a model of aggressive driving that incorporates the person-related and situational factors and the cognitive and emotional appraisal processes fundamental to driver aggression. In doing so, the research will assist to provide a clear definition of what constitutes aggressive driving, assist to identify on-road incidents that trigger driver aggression, and identify the emotional and cognitive appraisal processes that underlie driver aggression. Methods: The research involves three studies. Firstly, to contextualise the model and explore the cognitive and emotional aspects of driver aggression, a diary-based study using self-reports of aggressive driving events will be conducted with a general population of drivers. This data will be supplemented by in-depth follow-up interviews with a sub-sample of participants. Secondly, to test generalisability of the model, a large sample of drivers will be asked to respond to video-based scenarios depicting driving contexts derived from incidents identified in Study 1 as inciting aggression. Finally, to further operationalise and test the model an advanced driving simulator will be used with sample of drivers. These drivers will be exposed to various driving scenarios that would be expected to trigger negative emotional responses. Results: Work on the project has commenced and progress on the first study will be reported.

Comprehensive assessment of the fitness of older people for chemotherapy

Purpose: To present the results of a mixed-method study comparing the level of agreement of a two-phased, nurse-administered Comprehensive Geriatric Assessment (CGA) with current methods that assess the fitness for chemotherapy of older cancer patients. A nurse-led model of multidisciplinary cancer care based on the results is also described. Methods: The two phases comprised initial screening by a nurse with the Vulnerable Elders Survey-13 [VES-13], followed by nurse administration of a detailed CGA. Both phases were linked to a computerised algorithm categorising the patient as ‘fit’, ‘vulnerable’ or ‘frail’. The study determined the level of agreement between VES-13- and CGA-determined categories; and between the CGA and the physicians’ assessments. It also compared the CGA’s predictive abilities in terms of subsequent treatment toxicity; while interviews determined the acceptability of the nurse-led procedure from key stakeholders' perspectives. Results: Data collection was completed in December 2011. The results will be presented at the conference. A consecutive-series n=170 will be enrolled, 33% of whom are ‘fit’; 33% ‘vulnerable’; and 33% ‘too frail’ for treatment. This sample can detect, with 90% power, kappa coefficients of agreement of ≥ 0.70 or higher (“substantial agreement”). Fitness sub-group comparisons of agreement between the medical oncologist and the nurse assessments can detect kappa estimates of Κ ≥ 0.80 with the same power. Conclusion: The results have informed a nurse-led model of cancer care. It meets a clear need to develop, implement and test a nurse-led, robust, evidence-based, clinically-justifiable and economically-feasible CGA process that has relevance in national and international contexts.

Role of dentin matrix protein 1 in cartilage redifferentiation and osteoarthritis

Objective The aim of this study was to test the possible involvement, relevance and significance of dentin matrix protein 1 (DMP1) in chondrocyte redifferentiation and OA. Methods To examine the function of DMP1 in vitro, bone marrow stromal cells (BMSCs) and articular chondrocytes (ACs) were isolated and differentiated in micromasses in the presence or absence of DMP1 small interfering RNA and analysed for chondrogenic phenotype. The association of DMP1 expression with OA progression was analysed time dependently in the OA menisectomy rat model and in grade-specific OA human samples. Results It was found that DMP1 was strongly related to chondrogenesis, which was evidenced by the strong expression of DMP1 in the 14.5-day mouse embryonic cartilage development stage and in femoral heads of post-natal days 0 and 4. In vitro chondrogenesis in BMSCs and ACs was accompanied by a gradual increase in DMP1 expression at both the gene and protein levels. In addition, knockdown of DMP1 expression led to decreased chondrocyte marker genes, such as COL2A1, ACAN and SOX9, and an increase in the expression of COL10A and MMP13 in ACs. Moreover, treatment with IL-1β, a well-known catabolic culprit of proteoglycan matrix loss, significantly reduced the expression of DMP1. Furthermore, we also observed the suppression of DMP1 protein in a grade-specific manner in knee joint samples from patients with OA. In the menisectomy-induced OA model, an increase in the Mankin score was accompanied by the gradual loss of DMP1 expression. Conclusion Observations from this study suggest that DMP1 may play an important role in maintaining the chondrogenic phenotype and its possible involvement in altered cartilage matrix remodelling and degradation in disease conditions like OA.

An investigation approach to test protection intelligent electronic devices (IEDs) in IEC 61850 based substation automation systems (SAS) at station level

This thesis has developed a new approach to trace virtual protection signals in Electrical substation networks. The main goal of the research was to analyse the contents of the virtual signals transferred, using third party software. In doing so, a comprehensive test was done on a distance protection relay, using non-conventional test equipment.

A comprehensive ovine model of blood transfusion

Background The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. Results Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline–adenine–glucose–mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.